Herbs And Phytochemicals: Griffithsin - A Lectin Derived From The Red Algae Is Able To Inhibit Influenza A And SARS-CoV-2 Viruses

Herbs And Phytochemicals: The ongoing global challenges posed by infectious respiratory diseases, particularly those caused by influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlight the critical need for effective antiviral strategies. In this context, the emergence of the novel Omicron variant has further underscored the urgency of developing broad-spectrum antivirals capable of combating diverse viral strains. Among the promising candidates in this arena are griffithsin (GRFT) and its derivative, GL25E, derived from red algae (Griffithsia sp). These compounds exhibit potent inhibitory effects against both IAV and SARS-CoV-2, making them significant contenders in the search for effective antiviral therapies. A Herbs and Phytochemicals study conducted by researchers from Fudan University, Shanghai- China, Guiyang Maternal and Child Health Care Hospital, Guizhou,-China and the University of Calgary-Canada has found that the lectin Griffithsin and its derivative GL25E is able to not only inhibit influenza A viruses but also the SARS-CoV-2 virus and could be used not only as a therapeutic product but also as an effective prophylactic


Griffithsin - A Lectin Derived From The Red Algae Is Able To Inhibit Influenza A And SARS-CoV-2 Viruses
Schematic illustration of the mechanism by which GRFT and GL25E inhibit mono- or co-infection of IAV and SARS-CoV-2. GRFT or GRFT part in GL25E binds to the glycans on HA1 of IAV, thereby inhibiting IAV entry into the host cell. GL25E inhibits SARS-CoV-2 infection by binding via its GRFT part to glycans on S1 subunit of SARS-CoV-2 S protein and interacting via its EK1 part with HR1 domain in S2 subunit of SARS-CoV-2 S protein. GRFT (PDB code: 7RID).
 
Importance of Broad-Spectrum Antivirals
The significance of broad-spectrum antivirals cannot be overstated, especially in the context of respiratory viral infections like influenza and COVID-19. Co-infections involving IAV and SARS-CoV-2 can lead to heightened disease severity and complications, making the development of treatments capable of targeting multiple viruses simultaneously a critical endeavor in public health.
 
Understanding the Viral Proteins
Central to the development of effective antiviral agents is a deep understanding of the viral proteins involved in the infection process. Hemagglutinin (HA) in IAV and the spike (S) protein in SARS-CoV-2 play pivotal roles in mediating viral entry into host cells. Consequently, targeting these proteins, particularly their glycan-rich regions, has emerged as a promising strategy for the development of carbohydrate-binding protein-based antivirals.
 
Mechanism of Action
GRFT and GL25E exert their antiviral effects by targeting glycans present on HA and S proteins. By binding to these glycans, these compounds disrupt viral entry into host cells, thereby inhibiting the infection process. GL25E, distinguished by its bivalent structure, exhibits enhanced efficacy compared to GRFT alone, making it a particularly promising candidate for broad-spectrum antiviral therapy.
 
Inhibition of Influenza A Virus (IAV)
Extensive studies have demonstrated the potent inhibitory activity of both GRFT and GL25E against a spectrum of IAV strains in vitro. These compounds exhibit dose-dependent inhibition, with GL25E consistently demonstrating superior efficacy compared to GRFT alone. The ability of these compounds to effectively block IAV infection underscores their potential as valuable antiviral agents.
 
Protection Against IAV in Animal Models
In vivo experiments using animal models, particularly mice, have provided compelling evidence of the protective effects of GRFT and GL25E against lethal IAV infection. Administration of these compounds either prophylactically or therapeutically resulted in significantly improved survival rates and reduced lung damage, further supporting their potential as frontline antiviral therapies.
 
Mode of Inhibition
Detailed mechanistic studies, including time-of-addition assays and glycan interference studies, have elucidated the precise mode of action of GRFT and GL25E against IAV. These compounds primarily target HA1, disrupting viral entry at an early stage of infection. Their glycan-dependent inhibition highlights the importance of glycan interactions in the viral entry process and underscores the specificity of these compounds in targeting viral proteins.
 
Efficacy Against SARS-CoV-2 Omicron Variants
The emergence of SARS-CoV-2 variants, notably the Omicron variant, has presented new challenges in antiviral development. However, GRFT and GL25E have demonstrated robust inhibitory activity against a range of SARS-CoV-2 Omicron variants and subvariants in vitro. Notably, GL25E has shown superior efficacy compared to GRFT and EK1 alone, positioning it as a potent antiviral agent against evolving viral strains.
 
Inhibition of Co-Infection
Co-infections involving IAV and SARS-CoV-2 represent a significant clinical challenge, often leading to exacerbated disease severity. GL25E, with its enhanced efficacy against both viruses, has shown promising results in inhibiting co-infection in vitro. This dual-targeting capability makes GL25E a valuable asset in managing complex respiratory infections.
 
Safety and Stability Profiles
Apart from their efficacy, the safety and stability profiles of antiviral compounds are paramount in clinical applications. Both GRFT and GL25E have demonstrated favorable safety profiles in vitro and in vivo, with minimal cytotoxicity and no significant adverse effects observed in animal studies. Additionally, GL25E exhibits excellent stability under various storage conditions, further enhancing its suitability as a potential therapeutic agent.
 
Future Prospects
The promising efficacy, safety, and stability profiles of GRFT and GL25E position them as frontrunners in the development of broad-spectrum antivirals. Further research aimed at elucidating their mechanisms of action, optimizing dosing regimens, and conducting clinical trials will be crucial in harnessing their full therapeutic potential. With the ongoing evolution of viral strains and the persistence of respiratory viral infections, the development of versatile antiviral agents like GL25E represents a significant step forward in combating infectious diseases on a global scale.
 
Conclusion
In conclusion, the exploration of natural compounds like GRFT and its derivative GL25E as potent antiviral agents marks a promising advancement in infectious disease therapeutics. Their ability to target multiple viral proteins, inhibit co-infections, and maintain favorable safety profiles positions them as valuable assets in the ongoing battle against respiratory viral infections. As research progresses and clinical trials are conducted, these compounds hold the potential to significantly impact public health outcomes by offering effective and versatile treatments for influenza, COVID-19, and potentially other emerging respiratory viruses.
 
The study findings were published in the peer reviewed journal: mBIO.
https://journals.asm.org/doi/10.1128/mbio.00741-24
 
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